1. Field of Invention
The present invention relates generally to a method of producing porous structures, particles or matrixes, an apparatus for carrying out the method and porous particles formed in accordance with the method.
2. Description of Related Art
Porous or hollow particles of pure pharmaceuticals and composite particles, which can also contain one or more excipients such as biodegradable polymers, are desired for various drug delivery applications. Ideally, such particles would have low bulk density, reduced inter-particle interactions and good aerosol properties making them optimal for respiratory inhalable formulations. For instance solid porous drug particles in the aerodynamic size range between 1-5 microns having a geometric volume diameter between 1 and 20 microns are required for improved delivery of therapeutic agents to the respiratory tract. Further increased interest in recent years in gene therapy and needle free administration of proteins and vaccines has also prompted the need for preparation of composite porous particles for delivery through the respiratory route. Other drug delivery applications may include the drug-encapsulated porous or hollow particles as well as implantable porous polymeric matrixes for controlled or sustained release, and bioactive scaffolds for cell growth and tissue engineering.
Conventional techniques predominantly used in the pharmaceutical industry for producing porous materials include liquid phase antisolvent precipitation, freeze-drying and bleaching of composite matrixes with water or organic solvents. Unfortunately these techniques often incur various limitations during processing, the most important of which are poor control over residual solvents, adverse liquid solvents effect on chemical and physical stability of the porous materials produced, and chemical and thermal degradation due to use of high temperature or shear.
In recent years supercritical fluids (SCFs) have been effectively used to precipitate porous particles, more specifically porous particles of biodegradable polymers and drug composites. SCFs or compressed gasses or liquids (collectively referred to here after as “SCFs”) offer several advantages such as efficient extractions, mild operating conditions and clean environmentally benign processing.
The conventional supercritical fluid (SCF) techniques used for porous particle productions include the SCF antisolvent technique and its variations and the particles from expansion of SCF saturated technique. The porosity of the particles produced via both techniques is imparted due to diffusion into the atmosphere of the SCF dissolved in the biodegradable polymer matrix upon depressurization. The main disadvantage of both these techniques is that the process is limited to materials in which SCF can readily diffuse, namely a select few biodegradable polymers. In the antisolvent process, even if the SCF is readily soluble in the polymer, operating conditions must be selected such that dissolution of the SCF in the polymer does not cause plasticization of the polymer leading to melting and agglomeration of the polymer particles.
In view of the limitations of the conventional techniques, the present invention provides a new technique for producing porous structures such as particles, which can comprise only a single material such as a pure drug or can comprise a plurality of materials such as a drug and an excipient. The method offers precise control over the material bulk density, degree of porosity and pore size for various applications.